Alterations in inflammatory markers after a 12-week exercise program in individuals with schizophrenia—a randomized controlled trial

Background: In individuals with schizophrenia, inflammation is associated with depression, somatic comorbidity and reduced quality of life. Physical exercise is known to reduce inflammation in other populations, but we have only limited knowledge in the field of schizophrenia. We assessed inflammatory markers in plasma samples from individuals with schizophrenia participating in an exercise intervention randomized controlled trial. We hypothesized that (i) physical exercise would reduce levels of inflammatory markers and (ii) elevated inflammatory status at baseline would be associated with improvement in cardiorespiratory fitness (CRF) following intervention. Method: Eighty-two individuals with schizophrenia were randomized to a 12-week intervention of either high-intensity interval training (HIIT, n = 43) or active video gaming (AVG, n = 39). Participants were assessed at baseline, post intervention and four months later. The associations between exercise and the inflammatory markers soluble urokinase plasminogen activator receptor, c-reactive protein, tumor necrosis factor (TNF), soluble TNF receptor 1 and interleukin 6 (IL-6) were estimated using linear mixed effect models for repeated measures. For estimating associations between baseline inflammation and change in CRF, we used linear regression models. Results: Our main findings were (i) TNF and IL-6 increased during the intervention period for both groups. Other inflammatory markers did not change during the exercise intervention period; (ii) baseline inflammatory status did not influence change in CRF during intervention, except for a positive association between baseline IL-6 levels and improvements of CRF to post intervention for both groups. Conclusion: In our study, HIIT and AVG for 12-weeks had no reducing effect on inflammatory markers. Patients with high baseline IL-6 levels had a positive change in CRF during intervention. In order to increase our knowledge regarding association between inflammatory markers and exercise in individuals with schizophrenia, larger studies with more frequent and longer exercise bout duration are warranted

Exploring low grade inflammation by soluble urokinase plasminogen activator receptor levels in schizophrenia: a sex-dependent association with depressive symptoms

Background - There is evidence of increased low grade inflammation (LGI) in schizophrenia patients. However, the inter-individual variation is large and the association with demographic, somatic and psychiatric factors remains unclear. Our aim was to explore whether levels of the novel LGI marker soluble urokinase plasminogen activator receptor (suPAR) were associated with clinical factors in schizophrenia and if such associations were sex-dependent. Method - In this observational study a total of 187 participants with schizophrenia (108 males, 79 females) underwent physical examination and assessment with clinical interviews (Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale for Schizophrenia (CDSS), Alcohol Use Disorder Identification Test (AUDIT), and Drug Use Disorder Identification Test (DUDIT)). Blood levels of suPAR, glucose, lipids, and high sensitivity C-reactive protein (hsCRP) were determined and body mass index (BMI) calculated. Multivariable linear regression analyses were used adjusting for confounders, and sex interaction tested in significant variables. Results - Adjusting for sex, age, current tobacco smoking and BMI, we found that levels of hsCRP and depressive symptoms (CDSS) were positively associated with levels of suPAR (p  Conclusion - Our findings indicate that increased suPAR levels are associated with depressive symptoms in females with schizophrenia, suggesting aberrant immune activation in this subgroup. Our results warrant further studies, including longitudinal follow-up of suPAR levels in schizophrenia and experimental studies of mechanisms

Body language reading of emotion and outcome in schizophrenia

Introduction: Although considered a promising design for testing social cognition, it is not clear to what extent the EmoBio test of emotion recognition actually predicts community functioning. It is also not clear whether the test measures something unique or different from nonsocial cognition. The present study tests whether EmoBio accounts for GAF function score and two operationalised community outcome measures. The study also analyses cognitive predictors of EmoBio performance, testing whether stimulus modality affects prediction. Methods: Eighty-three patients with schizophrenia were tested with EmoBio, the cognitive battery MCCB and WAIS-IV. Results: EmoBio accounted for a significant portion of variance in all three outcome measures. Only EmoBio predicted Lifetime Relationship status, and EmoBio remained a significant predictor of Independent living beyond non-social cognition. All cognitive measures contributed significantly to the variance in EmoBio, but entered together explained only a third of total variance. Conclusion: The study shows that emotion recognition accounts for community outcome. There was no clear effect of test-modality in predicting EmoBio performance, indicating no method invariance problem with EmoBio. It also indicates that the mechanisms underlying impaired social cognition in schizophrenia are different from the hypothesised non-verbal learning deficits in the disorder

Effect of high-intensity interval training on cardiorespiratory fitness, physical activity and body composition in people with schizophrenia: a randomized controlled trial

Background Exercise may improve cardiorespiratory fitness in people with schizophrenia, however, possible condition-specific cardiorespiratory disadvantages, a scarcity of methodologically sound studies, and conflicting results raise questions about the effect of exercise on maximal oxygen uptake (VO2max) in this group. The primary aim of this study, therefore, was to investigate the effect of high-intensity interval training on VO2max in people with schizophrenia. Second, we sought to determine whether the intervention would have an effect on general physical activity (PA) level and body composition. Methods Eighty-two patients with schizophrenia were randomly assigned to supervised high-intensity interval training or computer gaming skills training, performed twice a week for 12 weeks. Oxygen uptake was measured directly, during a maximum exercise session on a treadmill. PA level were assessed using ActiGraph accelerometer, and body composition was assessed by bioelectrical impedance. Differences between groups were assessed by analysis of variance using a univariate general linear model. Results There were no significant differences between the groups on any of the cardiorespiratory variables neither at baseline nor after the program. There were also no significant within-group differences in any of the cardiorespiratory fitness variables between the baseline and post-program time points, despite that 61% of the participants performing high-intensity interval training showed a significant increase in workload on the treadmill. However, 47% of the participants in the high-intensity interval training group had a ≥ 5% increase in VO2max. Participants supervised by mental health care providers with PA competence (e.g. rehabilitation center staff, sport scientist, physical trainer) had a much larger increase in VO2max compared to participants supervised by mental health workers without such competence, and when adding PA competence to the model, the intervention group increased VO2max significantly compared to the comparison group. The intervention had no significant effect on PA level or body composition. Conclusions The intervention did not improve VO2max, PA level or body composition but succeeded in increasing workload on the treadmill. With regard to VO2max, approximately half of the patients may be considered responders

The Association Between Cardiorespiratory Fitness and Cognition Appears Neither Related to Current Physical Activity Nor Mediated by Brain-Derived Neurotrophic Factor in a Sample of Outpatients With Schizophrenia

Objective: We investigated whether levels of current physical activity (PA) contribute to the established relationship between cardiorespiratory fitness (CRF) and cognition in schizophrenia and whether brain-derived neurotrophic factor (BDNF) or its precursor proBDNF mediates this relationship. Method: Sixty-one outpatients with schizophrenia spectrum disorders participated. Neurocognition was assessed with the Wechsler Adult Intelligence Scale (WAIS) and nine subtests from the MATRICS battery comprising a neurocognitive composite score (NCS). CRF was assessed with peak oxygen uptake (VO2peak) measured directly during a maximum exercise test. Current PA levels were objectively assessed by an accelerometer worn for four consecutive days. BDNF and proBDNF were measured in fasting blood. Four serial parallel mediation analyses and two additional parallel mediation analyses were conducted, while controlling for age and sex at all levels. Results: No direct effects were found between PA measures and WAIS or NCS. No significant mediating effects of CRF or BDNF/proBDNF were detected. Conclusion: The results do not support the hypothesis that PA contributes to the naturally occurring relationship between CRF and cognition in schizophrenia or the hypothesis that BDNF or proBDNF mediates this relationship. The results arguably support the assumption that the association between CRF and cognition in schizophrenia is established developmentally early

Cardio-respiratory fitness is associated with a verbal factor across cognitive domains in schizophrenia

Abstract Objective We investigated whether the relationship between cardio-respiratory fitness (CRF) and cognition in schizophrenia is general, or due to selective relationships between CRF and specific aspects of cognitive function. Method Eighty outpatients with schizophrenia spectrum disorders participated. Neurocognition was assessed with the Wechsler Adult Intelligence Scale version 4 General Ability Index (WAIS GAI), the MATRICS Consensus Cognitive Battery (MCCB) and the Emotion in Biological Motion (EBM) test. CRF was assessed with peak oxygen uptake measured directly during maximum exercise using a modified Balke protocol. Partial correlations, controlling for sex and age, were obtained for the perceptual and the verbal indices of WAIS GAI, six cognitive domains of MCCB, and the EBM total score. A factor analysis was conducted on all 15 subtests of the WAIS GAI and the MCCB, and the factors were subjected to separate regression analyses with CRF as predictor. Results Significant, moderately sized correlations were found between CRF and all cognitive domains except processing speed. The correlation appeared strongest for CRF and the Verbal Comprehension Index of WAIS GAI (r = 0.29, p = .005). The factor analysis identified three factors: one speed/attention/executive function factor, one verbal factor, and one perceptual factor. Regression analyses showed that VO2peak explained a significant amount of variance in the verbal factor only (R2 = 0.06, β = 0.329, p = .03). Conclusion The results indicate that the relationship between CRF and cognition in schizophrenia is selectively tied to a modality-specific association with verbal cognitive abilities. These findings have implications for understanding the relation between cognitive factors and physical health in schizophrenia

The Association Between Cardiorespiratory Fitness and Cognition Appears Neither Related to Current Physical Activity Nor Mediated by Brain-Derived Neurotrophic Factor in a Sample of Outpatients With Schizophrenia

Objective: We investigated whether levels of current physical activity (PA) contribute to the established relationship between cardiorespiratory fitness (CRF) and cognition in schizophrenia and whether brain-derived neurotrophic factor (BDNF) or its precursor proBDNF mediates this relationship. Method: Sixty-one outpatients with schizophrenia spectrum disorders participated. Neurocognition was assessed with the Wechsler Adult Intelligence Scale (WAIS) and nine subtests from the MATRICS battery comprising a neurocognitive composite score (NCS). CRF was assessed with peak oxygen uptake (VO2peak) measured directly during a maximum exercise test. Current PA levels were objectively assessed by an accelerometer worn for four consecutive days. BDNF and proBDNF were measured in fasting blood. Four serial parallel mediation analyses and two additional parallel mediation analyses were conducted, while controlling for age and sex at all levels. Results: No direct effects were found between PA measures and WAIS or NCS. No significant mediating effects of CRF or BDNF/proBDNF were detected. Conclusion: The results do not support the hypothesis that PA contributes to the naturally occurring relationship between CRF and cognition in schizophrenia or the hypothesis that BDNF or proBDNF mediates this relationship. The results arguably support the assumption that the association between CRF and cognition in schizophrenia is established developmentally early

Objectively Assessed Daily Steps—Not Light Intensity Physical Activity, Moderate-to-Vigorous Physical Activity and Sedentary Time—Is Associated With Cardiorespiratory Fitness in Patients With Schizophrenia

People with schizophrenia often have an unhealthy sedentary lifestyle with low level of physical activity and poor cardiorespiratory fitness—an important predictor of cardiovascular disease. We investigated the relations between cardiorespiratory fitness and both sedentary time and different aspects of physical activity, such as daily steps, light intensity physical activity, and moderate-to-vigorous physical activity. Using accelerometer as an objective measure of sedentary time and physical activity we estimated their relations to cardiorespiratory fitness in 62 patients with schizophrenia with roughly equal gender distribution, mean age of 36 and 15 years illness duration. We found a significant association between daily steps and cardiorespiratory fitness when accounting for gender, age, sedentary time, light intensity physical activity, and respiratory exchange ratio (maximal effort). Moderate-to-vigorous physical activity was not significantly associated with cardiorespiratory fitness. In conclusion, the amount of steps throughout the day contributes to cardiorespiratory fitness in people with schizophrenia, independently of light intensity physical activity and sedentary time. We did not find a significant relationship between moderate-to-vigorous physical activity and cardiorespiratory fitness. This may have implications for the choice of strategies when helping patients with schizophrenia improve their cardiorespiratory fitness

Physical activity pattern and cardiorespiratory fitness in individuals with schizophrenia compared with a population-based sample

Objective: Thorough description of objectively assessed physical activity (PA) and sedentary time in people with schizophrenia is lacking, and previous studies comparing PA and cardiorespiratory fitness levels with healthy controls are limited by their small sample size and/or poor methodology. Method: PA, sedentary behavior, and cardiorespiratory fitness level were assessed in 67 adults diagnosed with schizophrenia (EPHAPS study) and compared with a population-based sample of 2809 adults (NPASS study). Results: Fifty-five percent of the participants with schizophrenia had the unhealthy combination of not meeting the PA recommendations and sitting >7.5 h per day compared to 32% in the population-based sample. The PA level was especially low on weekday afternoons and evenings and throughout most of the day on weekends. The peak oxygen uptake for EPHAPS women was on average 23% lower than that for NPASS women, while EPHAPS men achieved on average 34% lower oxygen uptake on the exercise test compared with NPASS men. Conclusion: People with schizophrenia are significantly less physically active, more sedentary, and have a poorer cardiorespiratory fitness level compared with the general population. Tailor-made PA interventions for people with schizophrenia should target their PA and sedentary behavior on afternoons and weekends especially

Physical activity pattern and cardiorespiratory fitness in individuals with schizophrenia compared with a population-based sample

Objective: Thorough description of objectively assessed physical activity (PA) and sedentary time in people with schizophrenia is lacking, and previous studies comparing PA and cardiorespiratory fitness levels with healthy controls are limited by their small sample size and/or poor methodology. Method: PA, sedentary behavior, and cardiorespiratory fitness level were assessed in 67 adults diagnosed with schizophrenia (EPHAPS study) and compared with a population-based sample of 2809 adults (NPASS study). Results: Fifty-five percent of the participants with schizophrenia had the unhealthy combination of not meeting the PA recommendations and sitting >7.5 h per day compared to 32% in the population-based sample. The PA level was especially low on weekday afternoons and evenings and throughout most of the day on weekends. The peak oxygen uptake for EPHAPS women was on average 23% lower than that for NPASS women, while EPHAPS men achieved on average 34% lower oxygen uptake on the exercise test compared with NPASS men. Conclusion: People with schizophrenia are significantly less physically active, more sedentary, and have a poorer cardiorespiratory fitness level compared with the general population. Tailor-made PA interventions for people with schizophrenia should target their PA and sedentary behavior on afternoons and weekends especially